Piezo2 感知呼吸道伸展,并调解肺部膨胀引起的呼吸暂停
Keiko Nonomura1, Seung-Hyun Woo1, Rui B Chang2
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA.
Nature
|December 22, 2016
概括
机械激活的离子通道Piezo2对于呼吸至关重要. 它的缺失导致新生儿的呼吸衰竭和成年人的呼吸异常,突出其在呼吸控制中的作用.
科学领域:
- 生理学
- 神经科学
- 分子生物学
背景情况:
- 呼吸功能障碍对婴儿死亡率和成人睡眠呼吸暂停有很大影响.
- 呼吸控制的精确机制,特别是来自呼吸道感觉神经元的机械信号,尚未完全理解.
- 机械激活的离子通道在这些过程中的作用仍然很模糊.
研究的目的:
- 研究机械激活的离子通道Piezo2在呼吸控制中的作用.
- 阐明呼吸道感官神经元中的Piezo2介导机械传导的生理意义和分子机制.
- 确定Piezo2对于从出生到成年正常呼吸的必要性.
主要方法:
- 在发育和成年小鼠中使用基因切除技术 (全局和感官神经元特异性) 来切除Piezo2.
- 在成年小鼠中使用光遗传来激活表达Piezo2的神经元.
- 评估了基因改造小鼠的呼吸功能,神经元对肺部膨胀的反应和赫林格-布鲁尔机械反射.
主要成果:
- 在新生小鼠中,Piezo2的切除导致呼吸困难和死亡.
- 在成年小鼠中,Piezo2+ 阴道感官神经元的光遗传激活诱导呼吸暂停.
- 成年感官神经元中的Piezo2损失损害了肺膨胀反应,削弱了海灵-布鲁尔反射,并增加了潮体积.
结论:
- Piezo2作为一个关键的气道伸展传感器.
- 在呼吸道抑制感官神经元中通过皮埃佐2介导的机械传导对于在出生时建立有效的呼吸是必不可少的.
- 这条通道对于维持正常的呼吸模式至关重要.
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